Tracheal Chondrosarcoma-A Novel Presentation of Lynch Syndrome.

This case report describes a man in his 60s with no cancer history who presented with 2 weeks of dysphagia, dysphonia, and a left neck mass.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

BACKGROUND AND OBJECTIVES: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery. METHODS: At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors. RESULTS: Naming decline occurred in 56% of patients and correlated with fMRI LI (r = -0.41, p < 0.001), age at epilepsy onset (r = -0.30, p = 0.006), age at surgery (r = -0.23, p = 0.039), and years of education (r = 0.24, p = 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points. DISCUSSION: An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.

Association of Celiac Disease With Pembrolizumab.

Immune checkpoint inhibitors (ICIs) in the recent times have transformed the landscape of the management of many solid tumors. Unfortunately, many immune-related adverse effects are associated with ICIs, which lead to a negative outcome in cancer treatment. We present a case of a 63-year-old female with metastatic adenocarcinoma of unknown origin, who developed celiac disease during the course of treatment with pembrolizumab. Association of celiac disease with this form of immunotherapy has never been documented before.

Patient Compliance With Maintenance Intravesical Therapy for Nonmuscle Invasive Bladder Cancer.

OBJECTIVE: To assess patient adherence to intravesical instillation therapy for nonmuscle invasive urothelial carcinoma outside of clinical trials. MATERIALS AND METHODS: We reviewed the records of patients from 2000 to 2013 who received intravesical therapy for nonmuscle invasive urothelial carcinoma. Patients with evidence of tumor recurrence or progression were excluded. We performed univariable and multivariable regression analyses to predict adherence to intravesical therapy. RESULTS: A total of 729 patients started 861 induction cycles, 63% with bacillus Calmette-Guèrin (BCG) and 37% with mitomycin C (MMC). The rate of completion of 6 weeks induction therapy with BCG and MMC was similar (86% and 87%, respectively). Within the BCG cohort, 161 (35%) patients commenced the Southwest Oncology Group (SWOG) maintenance protocol after induction and 16 (10%) completed all 21 treatments. A monthly protocol for BCG was started by 87 patients (19%) and 48 (55%) completed all 9 treatments. MMC therapy was started in 270 patients, 97 of whom (36%) commenced monthly maintenance treatment, and 46 (47%) completed treatments. Median number of instillations was 7 for patients undergoing monthly maintenance therapy (MMC or BCG) and 9 for patients allocated to 3 years BCG. On multivariable analysis, recurrence after prior treatment of urothelial carcinoma was predictive of patients' adherence to treatment. CONCLUSION: Compliance with intravesical therapy is low in clinical practice, notably for longer treatment schedules.

Cannabinoid Receptor 1 and Fatty Acid Amide Hydrolase Contribute to Operant Sensation Seeking in Mice.

A large body of evidence in humans and preclinical models supports a role for the endocannabinoid system in the proper execution of motivated or goal-directed behaviors. Operant sensation seeking (OSS) is a task that uses varied sensory stimuli as a reinforcer to maintain operant responding in mice. The purpose of the studies in this report was to begin to explore the role of endocannabinoid signaling in OSS utilizing cannabinoid receptor 1 (CB1R) and fatty acid amide hydrolase (FAAH) knock out mice. Compared to wild type littermate controls, CB1R knock out mice exhibited significantly fewer active responses and earned significantly fewer reinforcers in fixed ratio and progressive ratio schedules. On the other hand, FAAH knock out mice exhibited increased active responses and earned more reinforcers than wild type littermates in fixed ratio but not progressive ratio schedules. These findings support the role of endocannabinoid signaling in motivated behaviors and also expand our understanding of the signaling processes involved in OSS.

Treatment of ureteral anastomotic strictures with reimplantation and survival after cystectomy and urinary diversion.

OBJECTIVE: To examine whether long-term renal function and overall survival outcomes vary according to management approach for ureteral anastomotic stricture (UAS) after cystectomy and urinary diversion. METHODS: We conducted a retrospective cohort study of patients with benign UAS following cystectomy and urinary diversion using our institutional database. We compared time to stricture, renal function, rates of renal loss, and overall survival between patients undergoing ureteral reimplantation vs. those undergoing nonoperative management (nephrostomy tube or ureteral stent). A multivariable Cox proportional hazard model was used to determine whether reimplantation was independently associated with overall survival. RESULTS: We identified 87 UAS in 69 patients. Reimplantation was performed in 26 patients (37.7%), and 43 patients (62.3%) were managed nonoperatively. The interval between cystectomy and stricture diagnosis was similar in the reimplanted and nonoperative groups (3.06 vs. 4.34mo, P = 0.42). The differences between baseline and follow-up creatinine levels (+0.40 vs.+0.40mg/dl, P = 0.72) and estimated glomerular filtration rate (-25.0 vs.-18.9ml/min/1.73m2, P = 0.66) were similar between groups, as were rates of renal loss (34.6% vs. 39.5%, P = 0.68); however, mortality was significantly higher in the nonoperative group. After multivariable adjustment, overall survival remained significantly higher among UAS patients who underwent reimplantation (adjusted hazard ratio [aHR] for risk of death = 0.32, 95% CI: 0.13-0.80). CONCLUSION: Reimplantation was associated with improved overall survival but not with improved long-term renal functional outcomes compared with nonoperative management. Nonrenal complications of nonoperative UAS management may play an important role in reducing longevity.

Symptom burden and information needs in prostate cancer survivors: a case for tailored long-term survivorship care.

OBJECTIVES: To determine the relationship between long-term prostate cancer survivors' symptom burden and information needs. PATIENTS AND METHODS: We used population-based data from the Michigan Prostate Cancer Survivor Study (2499 men). We examined unadjusted differences in long-term information needs according to symptom burden and performed multivariable logistic regression to examine symptom burden and information needs adjusting for patient characteristics. RESULTS: High symptom burden was reported across all domains (sexual 44.4%, urinary 14.4%, vitality 12.7%, bowel 8.4%, emotional 7.6%) with over half of respondents (56%) reporting they needed more information. Top information needs involved recurrence, relationships, and long-term effects. Prostate cancer survivors with high symptom burden more often searched for information regardless of domain (P < 0.05). High sexual burden was associated with greater need for information about relationships [odds ratio (OR) 2.05, 95% confidence interval (CI) 1.54-2.72] and long-term effects (OR 1.60, 95% CI 1.23-2.07). High bowel burden was associated with greater information need for long-term effects (OR 2.28, 95% CI 1.43-3.63). CONCLUSIONS: Long-term prostate cancer survivors with high symptom burden need more supportive information. Tailoring information to these needs may be an efficient approach to support the growing population of long-term prostate cancer survivors.

A Model to Optimize Followup Care and Reduce Hospital Readmissions after Radical Cystectomy.

PURPOSE: Radical cystectomy has one of the highest readmission rates across all surgical procedures at approximately 25%. We developed a mathematical model to optimize outpatient followup regimens for radical cystectomy. MATERIALS AND METHODS: We used delay-time analysis, a systems engineering approach, to maximize the probability of detecting patients susceptible to readmission through office visits and telephone calls. Our data source includes patients readmitted after radical cystectomy from the Healthcare Cost and Utilization Project State Inpatient Databases in 2009 and 2010 as well as from our institutional bladder cancer database from 2007 to 2011. We measured the interval from hospital discharge to the point when a patient first exhibits concerning symptoms. Our primary end point is 30-day hospital readmission. Our model optimized the timing and sequence of followup care after radical cystectomy. RESULTS: The timing of office visits and telephone calls is more important in detecting a patient at risk for readmission than the sequence of these encounters. Patients are most likely to exhibit concerning symptoms between 4 and 5 days after discharge home. An optimally scheduled office visit can detect up to 16% of potential readmissions, which can be increased to 36% with 1 office visit followed by 4 telephone calls. CONCLUSIONS: Our model improves the detection of concerning symptoms after radical cystectomy by optimizing the timing and number of outpatient encounters. By understanding how to design better outpatient followup care for patients treated with radical cystectomy we can help reduce the readmission burden for this population.

Griscelli Syndrome Type 3: Two New Cases and Review of the Literature.

A 3-year-old Arab boy with a history of hypoplastic left heart syndrome was referred to the pediatric dermatology clinic at Sheba Medical Center for evaluation of hypomelanosis, manifested by fair skin pigmentation and silvery-grey hair, eyebrows, and eyelashes. The child had one older brother with similar hypopigmentation and another older brother who had died of congenital heart disease. The child had no history of neurologic deficits or immunodeficiency and no additional findings on clinical evaluation.

Segmental neurofibromatosis presenting with congenital excessive skin folds.

Segmental neurofibromatosis (SNF) is a rare type of neurofibromatosis (NF-1) resulting from post-zygotic somatic mutations in the neurofibromin gene that leads to mosaicism. Reported manifestations of SNF include neurofibromas, freckling, or café-au-lait spots limited to a single body region or limb. We present a 5-month-old male referred to our clinic for evaluation of congenital excessive skin folds on the back. A mildly erythematous, poorly demarcated soft plaque was noted, consisting of excessive skin folds. A cluster of light brown hyperpigmented macules was seen overlying the plaque. A punch biopsy of the plaque confirmed a diagnosis of neurofibroma. Further investigation ruled out other manifestations of NF-1. The early onset of our patient's neurofibroma and its gross appearance with redundant skin folds are all unusual features. To our knowledge, congenital excessive skin folds found in a single tumor have not been previously described in the literature as a manifestation of SNF. Clinicians should be educated about the possibility of congenital localized skin folds in association with SNF in order to identify the disease in infancy and monitor any changes in neurofibroma pathology.

Understanding hospital readmission intensity after radical cystectomy.

PURPOSE: Hospital readmissions after radical cystectomy vary with respect to intensity in terms of impact on patients and health care systems. Therefore, we conducted a population based study to examine factors associated with increasing readmission intensity after radical cystectomy for bladder cancer. MATERIALS AND METHODS: Using SEER (Surveillance, Epidemiology, and End Results)-Medicare data we identified 1,782 patients who underwent radical cystectomy from 2003 to 2009. We defined readmission intensity in terms of length of stay (days) divided into quartiles of less than 3 (lowest), 3 to 4, 5 to 7 and more than 7 (highest). We used logistic regression to examine factors associated with readmission intensity. RESULTS: More than half of the patients with the highest intensity readmissions were readmitted within the first week and 77% were readmitted within 2 weeks of discharge. Patients with the highest intensity readmissions were similar in age, gender, race, socioeconomic status, pathological stage, comorbidity, neoadjuvant chemotherapy use and urinary diversion type compared to patients with the lowest intensity readmissions. After multivariable adjustment, complications during the index cystectomy admission (p <0.001), readmission week (p=0.04), and the interaction between index length of stay and discharge to a skilled nursing facility (p=0.04) were associated with the highest readmission intensity. CONCLUSIONS: Readmission intensity differs widely after discharge following radical cystectomy. As postoperative efforts to minimize the readmission burden increase, a better understanding of the factors that contribute to the highest intensity readmissions will help direct limited resources (eg telephone calls, office visits) toward high yield areas.

Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease.

BACKGROUND: Sudden cardiovascular death is increased in chronic kidney disease (CKD). Experimental CKD models suggest that angiogenesis and nitric oxide (NO) inhibitors induce myocardial fibrosis and microvascular dropout thereby facilitating arrhythmogenesis. We undertook this study to characterize associations of CKD with human myocardial pathology, NO-related circulating angiogenesis inhibitors, and endothelial cell behavior. METHODS: We compared heart (n=54) and serum (n=162) samples from individuals with and without CKD, and assessed effects of serum on human coronary artery endothelial cells (HCAECs) in vitro. Left ventricular fibrosis and capillary density were quantified in post-mortem samples. Endothelial to mesenchymal transition (EndMT) was assessed by immunostaining of post-mortem samples and RNA expression in heart tissue obtained during cardiac surgery. Circulating asymmetric dimethylarginine (ADMA), endostatin (END), angiopoietin-2 (ANG), and thrombospondin-2 (TSP) were measured, and the effect of these factors and of subject serum on proliferation, apoptosis, and EndMT of HCAEC was analyzed. RESULTS: Cardiac fibrosis increased 12% and 77% in stage 3-4 CKD and ESRD and microvascular density decreased 12% and 16% vs. preserved renal function. EndMT-derived fibroblast proportion was 17% higher in stage 3-4 CKD and ESRD (P trend = 0.02). ADMA, ANG, TSP, and END concentrations increased in CKD. Both individual factors and CKD serum increased HCAEC apoptosis (P=0.02), decreased proliferation (P=0.03), and induced EndMT. CONCLUSIONS: CKD is associated with an increase in circulating angiogenesis and NO inhibitors, which impact proliferation and apoptosis of cardiac endothelial cells and promote EndMT, leading to cardiac fibrosis and capillary rarefaction. These processes may play key roles in CKD-associated CV disease.

A quantitative comparison of the efferent projections of the anterior and posterior subdivisions of the medial amygdala in female mice.

In rodents, many aspects of sociosexual behavior are mediated by chemosignals released by opposite-sex conspecifics. These chemosignals are relayed via the main (MOS) and accessory olfactory systems (AOS) to the medial amygdala (Me). The Me is subdivided into anterior (MeA) and posterior (MeP) subnuclei, and lesions targeting these regions have different effects on proceptive courtship behaviors in female mice. Differential behavioral effects of MeA vs. MeP lesions could reflect a difference in the projections of neurons located in these Me subnuclei. To examine this question, we injected female mice with the anterograde tracer, Fluoro-Ruby into either the MeA or MeP and quantified labeled puncta in 11 forebrain target sites implicated in courtship behaviors using confocal fluorescence microscopy. We found that the MeP more densely innervates the medial and intermediate regions of the posterior bed nucleus of the stria terminalis (pBNST) and the posteromedial cortical amygdala (PMCo), while the MeA more densely innervates the horizontal diagonal band of Broca (HDB) and the medial olfactory tubercle (mOT), a region that may be a component of the circuitry responsible for olfactory-mediated motivated behaviors.

Circulating endoglin concentration is not elevated in chronic kidney disease.

BACKGROUND: Soluble endoglin, a TGF-ß receptor, plays a key role in cardiovascular physiology. Whether circulating concentrations of soluble endoglin are elevated in CKD or underlie the high risk of cardiovascular death associated with chronic kidney disease (CKD) is unknown. METHODS: Individuals with and without CKD were recruited at a single center. Estimated glomerular filtration rate (eGFR) was estimated using the modified MDRD study equation and the serum creatinine at the time of recruitment, and patients were assigned to specific CKD stage according to usual guidelines. Serum endoglin concentration was measured by ELISA and univariate and multivariable regression was used to analyze the association between eGFR or CKD stage and the concentration of soluble endoglin. RESULTS: Serum endoglin was measured in 216 patients including 118 with stage 3 or higher CKD and 9 individuals with end stage renal disease (ESRD). Serum endoglin concentration did not vary significantly with CKD stage (increase of 0.16 ng/mL per 1 stage increase in CKD, P = 0.09) or eGFR (decrease -0.06 ng/mL per 10 mL/min/1.73 m(2) increase in GFR, P = 0.12), and was not higher in individuals with ESRD than in individuals with preserved renal function (4.2±1.1 and 4.3±1.2 ng/mL, respectively). Endoglin concentration was also not significantly associated with urinary albumin excretion. CONCLUSIONS: Renal function is not associated with the circulating concentration of soluble endoglin. Elevations in soluble endoglin concentration are unlikely to contribute to the progression of CKD or the predisposition of individuals with CKD to develop cardiovascular disease.